スルフィンピラゾン

SOL IN ETHYL ACETATE, CHLOROFORM

SLIGHTLY SOL IN WATER, ALC, ETHER, MINERAL OILS

SLIGHTLY SOL IN FATS

1 G SOL IN 10 ML ACETONE & 10 ML 0.5 N NAOH

For more Solubility (Complete) data for SULFINPYRAZONE (6 total), please visit the HSDB record page.

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

136-137 °C

136-137 °C

MELTING POINT: 130-133 °C /D-FORM, L-FORM/

136 - 137 °C

3.25

PKA: 2.8

193.5 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

199.9 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

CRYSTALS FROM CHLOROFORM & HEPTANE; CRYSTALS FROM ETHANOL /D-FORM/; CRYSTALS /L-FORM/

SPECIFIC OPTICAL ROTATION: +67.1 DEG @ 22 °C/D (C= 2.04 IN ETHANOL); +109.3 DEG @ 25 °C/D (C= 0.5 IN CHLOROFORM) /D-/

SPECIFIC OPTICAL ROTATION: -64.2 DEG @ 23 °C/D (C= 2.14 IN ETHANOL); -104.5 DEG @ 26 °C/D (C= 0.5 IN CHLOROFORM) /L-/

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 70 reports by companies from 1 notifications to the ECHA C&L Inventory.

...URICOSURIC ACTION /OF SULFINPYRAZONE/ IS ADDITIVE TO THAT OF PROBENECID & PHENYLBUTAZONE BUT IS MUTUALLY ANTAGONISTIC TO THAT OF SALICYLATES. ... POSSESSES ABILITY TO DISPLACE OTHER ORG ANIONS THAT ARE BOUND EXTENSIVELY TO PLASMA PROTEINS...THUS ALTERING THEIR DISTRIBUTION TO TISSUES & THEIR RENAL EXCRETION...

...SULFINPYRAZONE MAY POTENTIATE ACTIONS OF INSULIN & ORAL HYPOGLYCEMIC AGENTS...

SULFINPYRAZONE MAY DISPLACE SULFONAMIDES FROM PLASMA PROTEIN BINDING SITES...

HYPERSENSITIVITY REACTIONS, USUALLY A RASH WITH FEVER, DO OCCUR.../OCCASIONALLY/

SIDE EFFECTS INCL UPPER GI DISTURBANCES...&, RARELY, ANEMIA, LEUKOPENIA, AGRANULOCYTOSIS, & THROMBOCYTOPENIA.

M - Musculo-skeletal system

QM - Musculo-skeletal system

Sulfinpyrazone's pharmacologic activity is the potentiation of the urinary excretion of uric acid. It is useful for reducing the blood urate levels in patients with chronic tophaceous gout and acute intermittent gout, and for promoting the resorption of tophi.

Sulfinpyrazone is an oral uricosuric agent (pyrazolone derivative) used to treat chronic or intermittent gouty arthritis. Sulfinpyrazone competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby facilitating urinary excretion of uric acid and decreasing plasma urate concentrations. This is likely done through inhibition of the urate anion transporter (hURAT1) as well as the human organic anion transporter 4 (hOAT4). Sulfinpyrazone is not intended for the treatment of acute attacks because it lacks therapeutically useful analgesic and anti-inflammatory effects. Sulfinpyrazone and its sulfide metabolite possess COX inhibitory effects. Sulfinpyrazone has also been shown to be a UDP-glucuronsyltransferase inhibitor and a very potent CYP2C9 inhibitor. Sulfinpyrazone is also known to be a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor as well as an inhibitor of several multridrug resistance proteins (MRPs).

...IN SUFFICIENT DOSAGE IS POTENT INHIBITOR OF RENAL TUBULAR REABSORPTION OF URIC ACID. ...SMALL DOSES MAY REDUCE EXCRETION...PRESUMABLY BY INHIBITING SECRETORY BUT NOT REABSORPTIVE TRANSPORT. BY COMPETITIVE INHIBITION...REDUCES RENAL TUBULAR SECRETION OF OTHER ORG ANIONS...AS PAH /PARA-AMINOHIPPURIC/ & SALICYLIC ACID.

MOST OF DRUG (90%) IN URINE IS UNCHANGED; REMAINDER IS ELIMINATED AS N1-P-HYDROXYPHENYL METABOLITE...

.../IN RAT/ 28%...IN URINE & 24%...IN FECES & BILE WAS FOUND AS P-HYDROXYSULFINPYRAZOLE.

Sulfinpyrazone has known human metabolites that include Sulfinpyrazone sulfone.

...WELL ABSORBED AFTER ORAL ADMIN. ...BOUND TO PLASMA PROTEINS...98-99%. T/2... IN PLASMA AFTER IV INJECTION IS ABOUT 3 HR. AFTER ORAL ADMIN...URICOSURIC EFFECT MAY PERSIST FOR...10 HR. ALTHOUGH LITTLE...IS AVAILABLE FOR FILTRATION @ GLOMERULUS, IT IS SECRETED BY PROXIMAL TUBULE & UNDERGOES LITTLE PASSIVE BACK DIFFUSION...

APPROX HALF OF ORALLY ADMIN DOSE APPEARS IN URINE WITHIN 24 HR. MOST OF DRUG (90%) IN URINE IS UNCHANGED; REMAINDER IS ELIMINATED AS...METABOLITE...

...RAPIDLY EXCRETED IN MAN, TOGETHER WITH P-HYDROXYLATED METABOLITE. PLASMA T/2...IN RATS...16.2 HR, &...18% OF IP DOSE...WAS EXCRETED INTO URINE. PLASMA T/2 IN MAN...BETWEEN 1 & 3 HR. MAIN ROUTE OF ELIMINATION IN RAT...FECES (68% OF DOSE)...CONSIDERABLE PORTION...EXCRETED IN BILE WAS REABSORBED FROM INTESTINAL TRACT.

...SULFINPYRAZONE...IS EXCRETED IN URINE OF RATS TO ONLY A SMALL EXTENT. ... CLEARED FROM CIRCULATION MAINLY THROUGH BILE...NO EVIDENCE OF ENTERO-HEPATIC CIRCULATION MECHANISM.

UNCHANGED DRUG /IN RAT/ WAS PRINCIPAL EXCRETION PRODUCT & ONLY 28%...IN URINE & 24%...IN FECES & BILE WAS FOUND AS P-HYDROXYSULFINPYRAZOLE. FAILURE OF RAT TO EXCRETE A HIGH PROPORTION OF THE DRUG IN URINE MAY BE RELATED TO ITS LACK OF URICOSURIC PROPERTIES IN THIS SPECIES.

SYNTHESIS: PFISTER, HAFLIGER, HELV CHIM ACTA 44, 232 (1961).

[2-(PHENYLSULFINYL)ETHYL]MALONIC ACID DIETHYL ESTER IS CONDENSED WITH HYDRAZOBENZENE WITH AID OF SOLN OF SODIUM ETHOXIDE IN ABSOLUTE ETHANOL. ... /ADDN/ XYLENE & HEATING @...130 DEG...ETHANOL...IS REMOVED. SULFINPYRAZONE IS ISOLATED BY SOLVENT EXTRACTION...& RECRYSTALLIZED FROM ETHANOL. US PATENT 2,700,671.